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Biomedical subjects

T Forster

Publications and source records attributed to T Forster.

At least 19 recordsLinked to original sources
PubMed2003

Experiments using microarray technology: limitations and standard operating procedures.

Microarrays are a powerful method for the global analysis of gene or protein content and expression, opening up new horizons in molecular and physiological systems. This review focuses on the critical aspects of acquiring meaningful data for analysis following fluorescence-based target hybridisation to arrays. Although microarray technology is adaptable to the analysis of a range of biomolecules (DNA, RNA, protein, carbohydrates and lipids), the scheme presented here is applicable primarily to customised DNA arrays fabricated using long oligomer or cDNA probes. Rather than provide a comprehensive review of microarray technology and analysis techniques, both of which are large and complex areas, the aim of this paper is to provide a restricted overview, highlighting salient features to provide initial guidance in terms of pitfalls in planning and executing array projects. We outline standard operating procedures, which help streamline the analysis of microarray data resulting from a diversity of array formats and biological systems. We hope that this overview will provide practical initial guidance for those embarking on microarray studies.

Animals↗
PubMed2002

Outcome after extended follow-up in a prospective study of operable breast cancer: key factors and a prognostic index.

In 1990, 215 patients with operable breast cancer were entered into a prospective study of the prognostic significance of five biochemical markers and 15 other factors (pathological/chronological/patient). After a median follow-up of 6.6 years, there were 77 recurrences and 77 deaths (59 breast cancer-related). By univariate analysis, patient outcome related significantly to 13 factors. By multivariate analysis, the most important of nine independent factors were: number of nodes involved, steroid receptors (for oestrogen or progestogen), age, clinical or pathological tumour size and grade. Receptors and grade exerted their influence only in the first 3 years. Progestogen receptors (immunohistochemical) and oestrogen receptors (biochemical) were of similar prognostic significance. The two receptors were correlated (r=+0.50, P=0.001) and displaced each other from the analytical model but some evidence for the additivity of their prognostic values was seen when their levels were discordant.

Biomarkers, Tumor↗
PubMed2002

[HER-2 and TOP 2A gene amplifications in urinary bladder carcinoma].

The HER-2/neu gene is frequently amplified in bladder cancer. Topoisomerase 2 Alpha (TOP2A) which is located nearby the HER-2/neu gene is an important molecular target for several anti cancer drugs. The frequency of TOP2A amplification in urinary bladder cancer is unknown. It was the aim of this study to determine the frequency of HER-2 and TOP2A amplification in urinary bladder cancer and to evaluate the association of these amplifications with tumor phenotype. For this purpose a tissue microarray containing 768 pTa, 425 pT1 and 571 pT2-4 carcinomas was analyzed by fluorescence in situ hybridization (FISH). Amplifications of both genes were significantly associated with advanced tumor stage and high grade. HER-2 amplification was found in 1.6% of pTa, 7.2% of pT1 and 13.8% of pT2-4 carcinomas (p < 0.0001). HER-2 amplification was present in only 1.1% of grade 1 and 0.8% of grade 2 tumors but in 14.2% of grade 3 tumors (p < 0.0001). TOP2A amplification was present in 0.7% pTa, 1.8% pT1 and 3.4% pT2-4 carcinomas (p < 0.0001). TOP2A was found in none of the grade 1, in 0.2% of grade 2 and 3.8% of grade 3 tumors (p < 0.0001). 1% of all analyzed tumors had simultaneously high level amplification of TOP2A and HER-2. Amplification of both genes were significantly associated with tumor specific survival if all tumors were analyzed together. Given the high frequency of HER-2 amplification in urinary bladder cancer, some of these tumors may respond favorable to Herceptin therapy. The TOP2A amplification status may influence response to anthracyclin treatment.

Antigens, Neoplasm↗
PubMed2001

Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade.

The number of genes suggested to play a role in cancer biology is rapidly increasing. To be able to test a large number of molecular parameters in sufficiently large series of primary tumours, a tissue microarray (TMA) approach has been developed where samples from up to 1000 tumours can be simultaneously analysed on one glass slide. Because of the small size of the individual arrayed tissue samples (diameter 0.6 mm), the question arises of whether these specimens are representative of their donor tumours. To investigate how representative are the results obtained on TMAs, a set of 2317 bladder tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from different areas of each tumour. Clinical follow-up information was available from 1092 patients. The histological grade and the Ki67 LI were determined for every arrayed tumour sample (4x2317 analyses each). Despite discrepancies in individual cases, the grade and Ki67 information obtained on minute arrayed samples were highly similar to the data obtained on large sections (p<0.0001). Most importantly, every individual association between grade or Ki67 LI and tumour stage or prognosis (recurrence, progression, tumour-specific survival) that was observed in large section analysis could be fully reproduced on all four replica TMAs. These results show that intra-tumour heterogeneity does not significantly affect the ability to detect clinico-pathological correlations on TMAs, probably because of the large number of tumours that can be included in TMA studies. TMAs are a powerful tool for rapid identification of the biological or clinical significance of molecular alterations in bladder cancer and other tumour types.

Adenocarcinoma↗
PubMed2001

Clinical value of left atrial appendage flow velocity for predicting of cardioversion success in patients with non-valvular atrial fibrillation.

BACKGROUND: Echocardiographic parameters for predicting cardioversion outcome in patients with non-valvular atrial fibrillation are not accurately defined. OBJECTIVE: To evaluate the role of left atrial appendage flow velocity detected by transoesophageal echocardiography for prediction of cardioversion outcome in patients with non-valvular atrial fibrillation enrolled in a prospective. multicentre, international study. METHODS: Four hundred and eight patients (257 males, mean age: 66 +/- 10 years) with non-valvular atrial fibrillation lasting more than 48 h but less than 1 year underwent transthoracic echocardiography and transoesophageal echocardiography before either electrical (n=324) or pharmacological (n=84) cardioversion. RESULTS: Cardioversion was successful in restoring sinus rhythm in 328 (80%) and unsuccessful in 80 patients (20%). Mean left atrial appendage peak emptying flow velocity was significantly higher in patients with successful than in those with unsuccessful cardioversion (32.4 +/- 17.7 vs 23.5 +/- 13.6 cm x s(-1); P<0.0001). At multivariate logistic regression analysis, three parameters proved to be independent predictors of cardioversion success: the atrial fibrillation duration <2 weeks (P=0.011, OR=4.9, CI 95%=1.9-12.7), the mean left atrial appendage flow velocity >31 cm x s(-1) (P=0.0013, OR=2.8, CI 95%=1.5-5.4) and the left atrial diameter <47 mm (P=0.093, OR=2.0, CI 95%=1.2-3.4). These independent predictors of cardioversion success outperformed other univariate predictors such as left ventricular end-diastolic diameter <58 mm, ejection fraction >56% and the absence of left atrial spontaneous echo contrast. CONCLUSION: In patients with non-valvular atrial fibrillation, measurement of the left atrial appendage flow velocity profile by transoesophageal echocardiography before cardioversion provides valuable information for prediction of cardioversion outcome.

Atrial Appendage↗
PubMed2001

Improved detection of Mycobacterium spp. using the Bactec MGIT 960 system.

Until 1987, the notification rate for mycobacterial infection was on the decline; however, it now appears to be increasing once more. The reason for this may be multifactoral and include improved reporting of diagnosed cases, increased infection of an ageing population, homelessness, immunosuppression (e.g. due to human immunodeficiency virus infection), and immigration of people from countries where tuberculosis is endemic. This rising incidence and the increasing importance of resistant organisms mean that rapid identification by the clinical microbiology laboratory is required, and this is where an automated detection system can be an advantage. Over a two-year period, 2743 clinical specimen were examined for Mycobacterium spp. using the Bactec MGIT 960, and 286 were positive. Time to detection ranged from three to 14 days (mean: 9.3 days), and M. tuberculosis was recovered from 214 (75.5%). Contamination rate was higher (8.6%) than with manual methods, however. On balance, the Bactec MGIT 960 system proved a valuable tool in the routine microbiology laboratory.

Bacteriological Techniques↗
PubMed2000

[The clinical value of coronary flow reserve in ischemic heart disease as measured by dipyridamole stress transesophageal echocardiography].

The relationship between coronary flow reserve and the result of coronarography was examined. 152 patients were investigated by stress transoesophageal echocardiography and coronary angiography. The value of coronary flow reserve was significantly lower in cases of significant coronary stenosis than in those patients who had a normal coronarography (in patients with left anterior descending coronary artery stenosis: 1.77 +/- 0.47 vs in cases with normal coronary angiogram: 3.19 +/- 1.15). There was no difference in the value of CFR in those cases where not only LAD stenosis but CX or RC stenosis was also found. The value of coronary flow reserve was significantly higher in RC or CX patients than that of LAD patients. In patients with positive stress and negative coronarography (X syndrome) the coronary flow reserve was 1.23 +/- 0.2, which value was significantly lower as compared to patients with significant coronary stenosis.

Adult↗
PubMed2000

[Impending paradoxical embolism].

The case history of a 49-year-old female patient is reported, who was operated on because of varicose vein in the left lower extremity. A few days after the operation serious signs of cerebrovascular insult appeared. The clinical picture and the result of an urgent transoesophageal echocardiography are described; a serpentine thrombus was found to be trapped in the patent foramen ovale. During continuous intravenous heparin treatment, the patient gradually recovered, but a residual neurological deficit could be detected on discharge from the hospital. Six days after the admission, repeated transoesophageal echocardiographic examination showed no signs of intracardiac thrombus. The clinical feature of the illness, the predisposing factors, the diagnostic and therapeutic possibilities are discussed.

Diagnosis, Differential↗
PubMed1997

Noninvasive monitoring of hemodynamic changes in acute pancreatitis in rabbits.

Hemodynamic parameters of experimental acute necrotizing pancreatitis (AP) were monitored by means of echocardiography in rabbits. Left ventricular (LV) systolic and diastolic parameters were determined before and 1, 3, 6, 12, 18, and 24 hr after injection of taurocholic acid in the pancreatic duct in AP animals. Temporary LV dilatation was observed 6 hr after the AP induction [LV end-diastolic (ED) diameter from 1.16 +/- 0.04 to 1.22 +/- 0.04 cm, P < 0.05, ED volume from 2.98 +/- 0.34 to 3.57 +/- 0.75 ml, P < 0.05] without decrease in systolic function. Cardiac output (CO) and stroke volume (StV) was increased in both groups 3 hr after the operation (from 0.53 +/- 0.15 to 0.71 +/- 0.06 L/min, P < 0.05 in AP), but in the AP animals it remained high. However, 24 hr after AP induction, both the CO and the StV were decreased significantly. The LV diastolic function was impaired 1 hr after AP induction, but had recovered after 12 hr. In conclusion, an early diastolic impairment followed by LV enlargement could be noninvasively observed in experimental AP in rabbits.

Acute Disease↗
PubMed1997

Changes in left ventricular mass during treatment with minoxidil and cilazapril in hypertensive patients with left ventricular hypertrophy.

Attainment of the regression of hypertension-associated left ventricular hypertrophy (LVH) seems to be a desirable goal of blood pressure (BP)-reducing therapy. Since antihypertensive drugs of differing types may exhibit markedly different abilities to modulate LVH, we examined the effects of the angiotensin-converting enzyme inhibitor cilazapril, and the potassium channel activator minoxidil, alone or in combination with each other, on the left ventricular mass (LVM) in patients with severe essential hypertension who had LVH detected by echocardiography. All patients received the same base therapy of bopindolol and guanfacine. After a run-in period, they were treated with: (1) cilazapril (n = 10); (2) minoxidil, combined with a diuretic (n = 10); or (3) both cilazapril and monoxidil (n = 6) for 12 months. The LVM index (LVMI; LVM per body surface area) was estimated every 3 months by means of echocardiography. Each kind of therapy decreased the arterial pressures to a similar degree. The 1-year treatment with the cilazapril-based regimen resulted in a significantly diminished LVMI (from a mean +/- s.d. of 173 +/- 38 to 152 +/- 22 g/m2; P < 0.05). On the other hand, the minoxidil-based therapy led to a significant increase in LVMI (from 148 +/- 19 to 170 +/- 35 g/m2; P < 0.05). There were no significant LVMI changes in patients receiving the combined, cilazapril + minoxidil-based treatment (172 +/- 34 vs the pretreatment 183 +/- 54 g/m2). The results confirm that long-term treatment with cilazapril is effective both in reducing BP and in reducing LVM. In spite of yielding a satisfactory reduction of BP, minoxidil therapy, even in combination with a diuretic and a beta-blocker, may lead to an aggravation of pre-existing LVH; this effect of minoxidil could be prevented by the simultaneous administration of cilazapril.

Adult↗
PubMed1996

[Effect of cilazapril in patients with essential hypertension: effect on cardiac hypertrophy].

Numerous antihypertensive drugs exist with different modes of action, which have a really effective impact on hypertension. The life expectancy of hypertensive patients is known to depend on the degree of damage caused to their target organs by the hypertension itself. Cardiovascular hypertrophy and its complications are considered to be among the major elements of this process. This work evaluates the effectiveness of the long-term treatment of essential hypertensive subjects (n = 10) with a long-acting ACE-inhibitor, cilazapril, as concerns their blood pressure and cardiac hypertrophy. Cilazapril given orally in a daily dose of 2.5 mg effectively lowered both the systolic (delta 30 mm Hg) and the diastolic (delta 19 mm Hg) blood pressure. No changes were found in body weight or heart rate, and only one side-effects (skin rash) was reported. Cilazapril considerably decreased the left ventricular mass and hence the hypertrophic index of hypertensive patients with cardiac hypertrophy, suggesting that ACE inhibitors are effective not only in lowering blood pressure and decreasing hypertrophy, but also in lowering the cardiac morbidity and mortality.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Feasibility of simultaneous Tc99m sestamibi and 2D-echo cardiac imaging during dobutamine pharmacologic stress. Preliminary results in a female population.

Feasibility of simultaneous 2D-Echo and SPECT Tc99m Sestamibi imaging during dobutamine infusion was evaluated in a female population with suspected coronary artery disease and scheduled for diagnostic coronary angiography. A total of 49 consecutive subjects were studied. Patients under continuous ECG and 2D-Echo monitoring underwent standard dobutamine infusion at increasing doses to a diagnostic end-point. Tc99m Sestamibi was administered at the peak of the dobutamine effect. With this approach, 35 patients were identified correctly by 2D-Echo (Sensitivity = 60.1%; Specificity = 83.3%; Agreement = 71.4%; k = 0.43). Perfusion imaging with Tc99m Sestamibi resulted in correctly identifying 41 patients (Sensitivity = 83%; Specificity = 84%; Agreement = 83.6%; k = 0.67). Combining information obtained from the two tests resulted in increased specificity (92%) and decreased sensitivity (64%). Simultaneous assessment of perfusion and function with Tc99m Sestamibi and 2D-Echo imaging during dobutamine administration is easily performed without added risk or discomfort to the patient. Tc99m Sestamibi appeared to be slightly superior to 2D-Echo for the detection of CAD in this population, but the difference does not reach conventional statistical significance. The combined use of the two independent tests did not substantially improve the diagnostic accuracy of each method.

Adult↗
PubMed1995

[15-year echocardiographic follow-up of acromegalic patients].

An echocardiographic follow-up of 25 patients (pts) was performed, after the first examinations in 1978-1979. 15 pts have died in the last 15 years (Group 1), while 10 still living (Group 2). In Group 1 either the impaired global left ventricular at the time of the first echocardiography predicted a high mortality i.e. there were only two pts with normal echocardiographic findings. The other 6 acromegalic pts with a "normal heart" have survived. The left ventricular hypertrophy of pts in Group 2 was observed to increase during the 15-year follow-up, because of the development of systemic hypertension. In conclusion, the echocardiographic findings are of a good predictive value in estimations of the survival rate in acromegalic pts.

Acromegaly↗
PubMed1995

Familial dilated cardiomyopathy: a worse prognosis compared with sporadic forms.

OBJECTIVE: To establish the time of onset of dilated cardiomyopathy (DCM) by review of annual chest x rays, which are obligatory in Hungary. DESIGN: A retrospective survey of chest x rays of a cohort of confirmed cases of DCM, to assess time of onset of cardiomegaly. Clinical course was compared by follow up over a mean of six years from the time of diagnosis. SUBJECTS: 240 patients with DCM (31 familial, 209 non-familial). Diagnosis was made by echocardiography in all cases and confirmed by coronary angiography and heart biopsy in some cases. MAIN RESULTS: At diagnosis, the mean age of the patients was 31.8 years in the familial group and 39.6 years in the non-familial group (P < 0.05). The time between the onset of cardiomegaly (cardiothoracic ratio > 0.45) and clinical diagnosis was 8.0 and 10.1 years respectively (P < 0.05). The six year survival was 6% in the familial group and 23% in the non-familial group (P < 0.05). CONCLUSIONS: The familial form of DCM is the more malignant form: it occurs at an earlier age and progresses more rapidly than non-familial DCM.

Adult↗
PubMed1995

[Use of hypnotherapy techniques within the scope of behavior therapy treatment of learning and behavior disorders in children--2 case reports].

Most of the children on our ward suffer from severe speech and language disorders, dyslexia, other learning disabilities and conduct disorders. We treated 10 selected children with cognitive behavior therapy combined with hypnotherapy. To demonstrate this treatment strategy we report on a 9-year-old girl and a 9-year-old boy from this group and give a short description of the hypnotic communication patterns used in conjunction with behavior therapy. The therapy combination proved to be a useful one. The children's social competence and learning motivation improved throughout the general therapeutic setting. The children's responses to relevant questionnaires confirmed these findings. Our results suggest that an increase in treatment efficacy can be achieved by using hypnotherapeutic patterns in conjunction with behavior therapy in the treatment of children with the disabilities mentioned.

Attention Deficit Disorder with Hyperactivity↗